Biology subjects

Pitt, J.

Publications and source records attributed to Pitt, J..

5 recordsLinked to original sources

bioRxiv2026

NTAD: A longitudinal neuroimaging dataset of Alzheimer's disease pathology

We introduce the New Therapeutics in Alzheimer's Disease (NTAD) dataset, a multi-modal and longitudinal imaging dataset from 70 biomarker-positive people with early dementia or Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD), assessed over 2.5 years, and 35 healthy controls assessed at baseline. The data include simultaneous magneto- and electro-encephalography (M/EEG), 3-Tesla structural and functional magnetic resonance imaging (MRI), Amyloid-beta; positron emission tomography (PET), fluid proteomic biomarkers in cerebrospinal fluid and blood, and a battery of clinical and neuropsychological assessments. 11C UCB-J PET was undertaken for a subset of participants. For people with AD, assessments were repeated at approximately three weeks, 15 months, and 28 months after baseline. The data can be accessed through the Dementias Platform UK (DPUK), including pre-processed M/EEG and T1 MRI in pseudonymised BIDS format. With the pressing need to develop treatments for slowing, reversing, and preventing AD, these data provide an opportunity for identifying and validating novel biomarkers of Alzheimer's disease neurophysiology, as well as understanding its treatable pathology.

neuroscience↗

bioRxiv2025

Robust and replicable effects of ageing on resting state brain electrophysiology measured with MEG.

Non-invasive recordings using brain electrophysiology provide credible insights into decline in neuronal functioning with age. New approaches are required to translate these results into compelling clinical metrics and meet the global challenge of preserving brain health in ageing. Changes in neuronal dynamics with ageing are observable in the power spectra of EEG and MEG recordings. Highly promising candidates for electrophysiological markers have been identified, but progress is hindered by substantial methodological variability across studies. This makes it challenging to establish a clear consensus on the frequency, location, and direction of any single reported effect within the larger body of research. We estimate a full-frequency whole-head profile of the ageing effect on eyes-closed resting-state MEG using the GLM-Spectrum. This data representation is easily sharable, facilitates meta-analyses and provides a framework for estimating statistical power of age effects for future study planning. We use this to show that the effect of age replicates across open-access MEG datasets and is robust to modelling of common covariates. Distinct components within the full frequency profile have different effect sizes, indicating that sample-size planning for ageing effects must consider the specific features of interest. The frequency profile of ageing is strongly robust to a range of common covariates and partially robust to modelling of grey matter volume. We establish that what seems a well-powered study may become underpowered when analyses target an age effect that is linearly separable from an age-relevant covariate such as grey matter volume. These results provide a pathway towards formal comparison and assessment of candidate markers for brain health in ageing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/668093v3_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1a9c351org.highwire.dtl.DTLVardef@563837org.highwire.dtl.DTLVardef@84b898org.highwire.dtl.DTLVardef@1730472_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThere is a strong effect of ageing across the adult lifespan on neuronal oscillations across a range of frequencies and spatial locations. C_LIO_LIThe effect is replicable across multiple open-access datasets. C_LIO_LIThe effect is robust to a range of sources of inter-subject variability. C_LIO_LIThe age effect has heterogeneous effect size across space and frequency with implications for future study planning. C_LI

neuroscience↗

bioRxiv2024

Effects of age on resting-state cortical networks

Understanding how ageing affects brain function remains a central challenge in neuroscience. Electrophysiological brain imaging techniques provide a near-direct measure of neuronal activity, which is useful for characterising neurophysiological health. They offer us the ability to track large-scale networks of functional activity with high temporal precision. The effects of healthy ageing on these networks remain poorly understood, in part due to small sample sizes and limited control for confounding factors in previous studies. Here, we analysed resting-state source-reconstructed magnetoencephalography (MEG) data from a large cross-sectional cohort of healthy adults (N =612, 18-88 years old) to characterise the effect of age using not only time-averaged (static), but also transient (dynamic) network activity. We examined time-averaged power and coherence across canonical frequency bands ({delta}, {theta}, , {beta}, {gamma}), as well as transient network dynamics identified using Hidden Markov Modelling. We included many confounding variables known to be affected by age, such as brain volume, as well as head size and position, which have previously been overlooked. Ageing was associated with frequency-specific changes in oscillatory power, with decreases in low-frequency ({delta}, {theta}) power and increases in high-frequency ({beta}) power. Coherence increased across all frequency bands and was positively associated with cognitive performance. Transient network analyses additionally revealed that frontal network occurrences declined with age, with evidence suggesting a compensatory role in supporting cognition. These findings provide a more comprehensive electrophysiological signature for healthy ageing and establish a baseline for detecting pathological change. HighlightsO_LIUsing source reconstructed magnetoencephalography data, we studied cortical functional networks of oscillatory activity from a large healthy population (612 subjects, 18-88 years old). C_LIO_LITime-averaged (static) network analysis in canonical frequency bands ({delta}, {theta}, , {beta}, {gamma}) showed: {beta} power and coherence increased with age; {delta}/{theta} power decreased with age, but coherence increased. Coherence in all frequencies increased with cognitive performance. C_LIO_LITransient (dynamic) network analysis showed frontal networks decreased in occurrence with age and their relation to cognitive performance showed that these changes were compensatory. The other networks showed a decreased occurrence with age. C_LIO_LIIn testing age and cognitive performance effects for statistical significance, we included a comprehensive set of confounds, such as brain volumes, head size and position, which has previously been overlooked. C_LIO_LIWe provide a comprehensive electrophysiological signature for healthy ageing and establish a baseline for detecting pathological change. C_LI

neuroscience↗

bioRxiv2023

Reliability of dynamic causal modelling of resting state magnetoencephalography

This study assesses the reliability of resting-state dynamic causal modelling (DCM) of magneto-electroencephalography under conductance-based canonical microcircuit models, in terms of both posterior parameter estimates and model evidence. We use resting state magneto-electroencephalography (MEG) data from two sessions, acquired two weeks apart, from a cohort with high between-subject variance arising from Alzheimers disease. Our focus is not on the effect of disease, but on the predictive validity of the methods implicit in their reliability, which is crucial for future studies of disease progression and drug intervention. To assess the predictive validity of first-level DCMs, we compare model evidence associated with the covariance among subject-specific free energies (i.e., the quality of the models) with vs. without interclass correlations. We then used parametric empirical Bayes (PEB) to investigate the predictive validity of DCM parameters at the between subject level. Specifically, we examined the evidence for or against parameter differences (i) within-subject, within-session, between-epochs; (ii) within-subject between-session and (iii) within-site between-subjects, accommodating the conditional dependency among parameter estimates. We show that for data acquired close in time, and under similar circumstances, more than 95% of inferred DCM parameters are unlikely to differ, speaking to mutual predictability over sessions. Using PEB, we show a reciprocal relationship between a conventional definition of reliability and the conditional dependency among inferred model parameters. Our analyses confirm the predictive validity and reliability of the conductance-based DCMs for resting-state neurophysiological data. In this respect, the implicit generative modelling is suitable for interventional and longitudinal studies of neurological and psychiatric disorders. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/562379v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@135c964org.highwire.dtl.DTLVardef@38e4a7org.highwire.dtl.DTLVardef@12bc358org.highwire.dtl.DTLVardef@25f110_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

The GLM-Spectrum: A multilevel framework for spectrum analysis with covariate and confound modelling

The frequency spectrum is a central method for representing the dynamics within electrophysiological data. Some widely used spectrum estimators make use of averaging across time segments to reduce noise in the final spectrum. The core of this approach has not changed substantially since the 1960s, though many advances in the field of regression modelling and statistics have been made during this time. Here, we propose a new approach, the General Linear Model (GLM) Spectrum, which reframes time averaged spectral estimation as multiple regression. This brings several benefits, including the ability to do confound modelling, hierarchical modelling and significance testing via non-parametric statistics. We apply the approach to a dataset of EEG recordings of participants who alternate between eyes-open and eyes-closed resting state. The GLM-Spectrum can model both conditions, quantify their differences, and perform denoising through confound regression in a single step. This application is scaled up from a single channel to a whole head recording and, finally, applied to quantify age differences across a large group-level dataset. We show that the GLM-Spectrum lends itself to rigorous modelling of within- and between-subject contrasts as well as their interactions, and that the use of model-projected spectra provides an intuitive visualisation. The GLM-Spectrum is a flexible framework for robust multi-level analysis of power spectra, with adaptive covariance and confound modelling.

neuroscience↗